Antimicrobial Therapy: Intro Flashcards
Antimicrobial Minimum Inhibitory Concentration
- Minimum inhibitory Concentration (MIC)
- Lowest concentration of antimicrobial needed to inhibit visible microbial growth
- Estimates susceptibility of specific bacteria to antimicrobials
MIC results
- Reported as:
- Susceptible: reasonable likelihood of success
- Intermediate: increases in dose may result in success or highly susceptible location in body
- Resistant: unlikely to result in clinical success
- Factors affecting susceptibility breakpoints
- animal species
- Bacteria
- Disease
- Drug
- Dose
- Route
- Frequency
Spectrum
The bacteria typically susceptible to an antimicrobial
Resistance:
Intrinsic
the bacteria were never susceptible to the antimicrobial
Resistance:
Acquired
at some point the bacteria were susceptible to the antimicrobial
Resistance
- We do NOT “cause” resistant mechanisms, we select for them
- The mechanisms are already often in the bacterial population or occur through spontaneous mutation independent of antimicrobial treatment
- when susceptible die off, the resistant strains are left and flourish
- Mechanisms of resistnace include:
- efflux pumps or decreased uptake
- inactivation of the antibiotic
- modify the target
- Resistance mechanisms may be shared within bacterial species or between bacterial species
Treatment Goals:
Therapeutic
clear the infection
Treathment Goals:
Prophylaxis / Prevention
Treating prior to bacterial exposure to prevent infection
Treatment Goals:
Growth Promotion
feeding antimicrobials decreases subclinical disease or alters microbiome resulting in more efficient feed conversions
Treatment Goal:
Do we need to treat?
- is there a benefit to treatment?
- Is there even an infection?
- A fever may not be due to an infection. It could be inflammation, hyperthermia
- Avoid/minimize adverse effects
- Avoid bacterial resistance selection
- Avoid violative residues in food animals
- Ensure client compliance
Bactericidal
antimicrobial kills bacteria
beta lactams, aminoglycosides, nirtoimidazoles, fluoroquinolones
Bacteriostatic
inhibit microbial growth
Tetracyclines, macrolides / lincosamides, sulfonamides, -phenicols
Pharmacodynamics - What is our target?
Peak / concentration dependent (CMAX:MIC)
- fluroquinolones, aminoglycosides, metronidazole
- Rate/extent of killing increase with increasing concnetrations, then plateaus at about 10X MIC
-
Post-antibiotic Effect (PAE):
- continued bacterial death / inhibition due to bacterial damage
Pharmacodynamics - What is our target?
Time above MIC (T>MIC)
- Beta Lactams, sulfas, -phenicols
- More important to maintain concentrations above MIC, but no major advantage to markedly exceeeding the MIC
Pharmacodynamics - What is our target?
AUC:MIC
- Tetracyclines, macrolides/lincosamides, fluorquinolones
- Total drug exposure over time
Pharmacokinetics - effect of dividing a total daily dose
- CMAX higher for once daily administration
- CMAX = 140 mcg/ml given every 24 hours
- CMAX = 70 mcg/ml given every 12 hours
- Important for concentration dependent
- Not so important for time dependent
- CMIN is lowe for once daily administration
- CMIN = 0.05 mcg/ml given every 24 hours
- CMIN = 1.5 mcg/ml given every 12 hours
- More dificult to maintian T > MIC
- Drug free interval decreases aminoglycoside renal toxicity
- AUC
- typically the same for either dosage
Routes of Administration:
Oral
- “Ease” of administration, typical lower cost, may increase GI adverse effects
- Fluoroquinolones, Macrolides / lincosamides, metronidazole, TMs
- Some: Beta lactams, -phenicols, tetracyclines
Routes of Administration:
Parenteral (IV, IM, SQ)
- May provide more consistent and higher concentrations than PO
- May increase client compliance
- Route for drugs with low bioavailability
- poor lipophilicity
- First pass metabolism
- Unstable in GIT
- Aminoglycosides, also same FQs, macrolides, -phenicols, tetracyclines
Routes of Administration:
Topical
- Higher concentrations at site of infection
- may enhance spectrum
- Less systemic adverse effects
- Drugs that are toxic systemically, may be applied topically
Routes of Elimination:
Metabolism
Hypically inactivates Macrolides, -phenicols
Routes of Elimination:
Biliary Secretion
may be active drug or inactive metabolite
Doxycycline
Routes of Elimination:
Renal Elimination
May result in high concentrations in the urine and increase efficacy for UTIs
Beta-lactams, aminoglycosides, trimethoprim, some tetracyclines, some fluoroquinolones
Drug penetration into protected tissues
CNS, prostate, eye, bronchi
- Limitaitons include:
- lipophilicity
- protein binding
- efflux transporters
- In general:
- fluoroquinolones
- -phenicols
- Trimethoprim / sulfonamide
- Some macrolides
- Some tetracyclines
- Some cephalosporins penetrate CNS/Prostate/Eye/ well
- cephalexin
Species Differences:
Horses
Many antimicrobials disrupt GIT flora, resulting in overgrwoth of pathogenic/opportunistic bacteria = sepsis and death
Many antimicrobials also have poor oral bioavailability
Conversely IV doxycycline is lethal, but can be administered PO
Species Differences:
cattle
Drug residues, compliance, resistance
Species Differences:
Dogs
Sulfonamides - autoimmune like reactions, KCS
Species Differences:
Cats
Fluoroquinolone retinal degeneration
Doxycycline, clindamycin esophageal stricture
Banned Drugs (Food Animal)
- Extralabel use prohibited:
- chloramphenicol - no label
- Nitroimidazoles - no label
- Fluoroquinolones
- Nitrofurazones - no label
- Glycopeptides - some label use
- Sulfonamides in lactating dairy cows over 20 months of age
- Cephalosporins - extralabel doses/routes prohibited, but therapeutic applications in unlaneled diseases OK
- applies to major species
- Minor species ELDU allowed, cephapirin intrammamary is an exception
Limitations of use:
Treatment Failure?
- Misdiagnosis
- incorrect dose / route / frequency
- Immunosuppression
- Compliance
- Underlying disease
- Foreign body / implant / nidus
- Pharmacokinetic interaction
- True antimicrobial resistance
- Reinfection vs. Failure
Limitations of Use:
Abscesses
antimicrobials are unlikely to be effective without drainage
Inability to penetrate and remain active at necessary concentrations
Limitations of use:
Pseudomonas spp.
- Most Pseudomonas are difficult to treat. If possible use topical
- PO effectively limited to Fluoroquinolones
- Ceftazidime, carbapenems, anti-pseudomonal penicillins, aminoglycosides
Limitations of Use:
Enterococcus spp.
- Amoxicillin >>> Tetracylines, chloramphenicols, rifampin, fluoroquinolones, nitrofurantoin
- Regardless of susceptibility testing, chephalosporins, trimethoprim sulfa, clindamycin, aminoglycosides, azithromycin are ineffective
- If resistant and a co-infection with Enterococcus, sometimes treating the other pathogens will result in clearance of Enterococcus spp.
